Annals of Nuclear Medicine

, Volume 24, Issue 9, pp 663–669 | Cite as

Imaging of a rat osteoarthritis model using 18F-fluoride positron emission tomography

  • Yusuke UmemotoEmail author
  • Takushi Oka
  • Tomio Inoue
  • Tomoyuki Saito
Original Article



Currently, conventional radiography is the standard method for the diagnosis and evaluation of the severity of osteoarthritis (OA), but it takes a couple of years to detect cartilage loss. Magnetic resonance imaging can delineate articular cartilage and accurately assess cartilage volume and thickness, but its reliability for very early diagnosis of OA is still controversial. The purpose of this study was to confirm the potential of 18F-fluoride PET for the early diagnosis of OA by using a surgically induced rat OA model.


Seventeen 16-week-old male Sprague-Dawley rats underwent anterior cruciate ligament transection (ACLT) in the right knee to induce OA. The left knee underwent sham operation. At 2, 4, and 8 weeks after operation, the rats were injected with 2.5 MBq/kg of 18F-fluoride, and 30 min after injection, each rat was killed and the bilateral knees were resected. The femur and tibia were cut horizontally, approximately 2 mm from the joint surface excluding the growth plate, and were cut into the medial and lateral condyles. The patella was also resected and blood samples were collected. The radioactivity of each sample was measured by gamma counting. Assays for serum cartilage oligomeric matrix protein and serum C-telopeptide of type II collagen were performed. Histopathological grading was performed according to a modified Mankin’s scoring system. Two rats underwent PET scans at 2, 4, and 8 weeks after operation. The rats were injected with 30 MBq of 18F-fluoride, and 30 min after injection, bilateral knee images with a 30-min acquisition time were obtained with an animal PET system.


The uptake of 18F-fluoride was significantly higher in ACLT knees than sham-operated knees in the medial femur and medial tibia at 2 weeks after operation. At 4 weeks after operation, the medial femur, medial tibia, and lateral tibia of OA knees showed significantly higher uptake of 18F-fluoride compared with sham-operated knees. At 8 weeks, all sections showed significant differences. The uptake of 18F-fluoride significantly increased as time elapsed in all sections. Uptake showed a significant correlation with histological scores.


Our results suggest that 18F-fluoride is potentially useful for the early detection of osteoarthritic changes.


Positron emission tomography 18F-fluoride Osteoarthritis Knee Rat model 


  1. 1.
    Kellgren JH, Lawrence JS. Radiological assessment of osteo-arthrosis. Ann Rheum Dis. 1957;16:494–502.CrossRefPubMedGoogle Scholar
  2. 2.
    Buckland-Wright. Radiographic assessment of osteoarthritis: comparison between existing methodologies. Osteoarthr Cartil. 1999;7:430–3.Google Scholar
  3. 3.
    Mazzuca SA, Brandt KD, Buckwalter KA, Lequesne M. Pitfalls in the accurate measurement of joint space narrowing in semiflexed, anteroposterior radiographic imaging of the knee. Arthritis Rheum. 2004;50:2508–15.CrossRefPubMedGoogle Scholar
  4. 4.
    Eckstein F, Schnier M, Haubner M, Priebsch J, Glaser C, Englmeier KH, et al. Accuracy of cartilage volume and thickness measurements with magnetic resonance imaging. Clin Orthop. 1998;352:137–48.PubMedGoogle Scholar
  5. 5.
    Burgkart R, Glaser C, Hyhlik-Durr A, Englmeier KH, Reiser M, Eckstein F. Magnetic resonance imaging-based assessment of cartilage loss in severe osteoarthritis: accuracy, precision, and diagnostic value. Arthritis Rheum. 2001;44:2072–7.CrossRefPubMedGoogle Scholar
  6. 6.
    Gray ML, Eckstein F, Peterfy C, Dahlberg L, Kim YJ, Sorensen AG. Toward imaging biomarkers for osteoarthritis. Clin Orthop. 2004;427:S175–81.CrossRefPubMedGoogle Scholar
  7. 7.
    Nakamura H, Masuko K, Yudoh K, Kato T, Nishioka K, Sugihara T, et al. Positron emission tomography with 18F-FDG in osteoarthritic knee. Osteoarthr Cartil. 2007;15(6):673–81.CrossRefPubMedGoogle Scholar
  8. 8.
    Costeas A, Woodard HQ, Laughlin JS. Depletion of 18F from blood flowing through bone. J Nucl Med. 1970;11:43–5.PubMedGoogle Scholar
  9. 9.
    Stoop R, Buma P, van der Kraan PM, Hollander AP, Clark Billinghurst R, Robin Poole A, et al. Differences in type II collagen degeneration between peripheral and central cartilage of rat stifle joints after cranial cruciate ligament transaction. Arthritis Rheum. 2000;43:2121–31.CrossRefPubMedGoogle Scholar
  10. 10.
    Cake MA, Read RA, Guillou B, Ghosh P. Modification of articular cartilage and subchondral bone pathology in an ovine meniscectomy model of osteoarthritis by avocado and soya unsaponifiables (ASU). Osteoarthr Cartil. 2000;8:404–11.CrossRefPubMedGoogle Scholar
  11. 11.
    Little C, Smith S, Ghosh P, Bellenger C. Histomorphological and immunohistochemical evaluation of joint changes in a model of osteoarthritis induced by lateral meniscectomy in sheep. J Rheumatol. 1997;24:2199–209.PubMedGoogle Scholar
  12. 12.
    Wenz W, Breusch SJ, Graf J, Stratmann U. Ultrastructural findings after intraarticular application of hyaluronan in a canine model of arthropathy. J Orthop Res. 2000;18:604–12.CrossRefPubMedGoogle Scholar
  13. 13.
    Blau M, Nagler W, Bender MA. Fluorine-18: a new isotope for bone scanning. J Nucl Med. 1962;3:332–4.PubMedGoogle Scholar
  14. 14.
    French RJ, McCready VR. The use of 18-F for bone scanning. Br J Radiol. 1967;40:655–61.CrossRefPubMedGoogle Scholar
  15. 15.
    Hawkins RA, Choi Y, Huang SC, Hoh CK, Dahlbom M, Schiepers C, et al. Evaluation of the skeletal kinetics of fluorine-18-fluoride ion with PET. J Nucl Med. 1992;33:633–42.PubMedGoogle Scholar
  16. 16.
    Schiepers C, Nuyts J, Bormans G, Dequeker J, Bouillon R, Mortelmans L, et al. Fluoride kinetics of the axial skeleton measured in vivo with fluorine-18-fluoride PET. J Nucl Med. 1997;38:1970–6.PubMedGoogle Scholar
  17. 17.
    Bashir A, Gray ML, Burstein D. Gd-DTPA2—as a measure of cartilage degradation. Magn Reson Med. 1996;36(5):665–73.CrossRefPubMedGoogle Scholar
  18. 18.
    Bashir A, Gray ML, Hartke J, Burstein D. Nondestructive imaging of human cartilage glycosaminoglycan concentration by MRI. Magn Reson Med. 1999;41(5):857–65.CrossRefPubMedGoogle Scholar
  19. 19.
    Nieminen MT, Rieppo J, Töyräs J, Hakumäki JM, Silvennoinen J, Hyttinen MM, et al. T2 relaxation time reveals spatial collagen architecture in articular cartilage: a comparative quantitative MRI and polarized light microscopic study. Magn Reson Med. 2001;46(3):487–93.CrossRefPubMedGoogle Scholar
  20. 20.
    Smith HE, Mosher TJ, Dardzinski BJ, Collins BG, Collins CM, Yang QX, et al. Spatial variation in cartilage T2 of the knee. J Magn Reson Imaging. 2001;14(1):50–5.CrossRefPubMedGoogle Scholar
  21. 21.
    Wandler E, Kramer EL, Sherman O, Babb J, Scarola J, Rafii M. Diffuse FDG shoulder uptake on PET is associated with clinical findings of osteoarthritis. Am J Roentgenol. 2005;185(3):797–803.Google Scholar
  22. 22.
    Kubota K, Ito K, Morooka M, Mitsumoto T, Kurihara K, Yamashita H, et al. Whole-body FDG-PET/CT on rheumatoid arthritis of large joints. Ann Nucl Med. 2009;23:783–91.CrossRefPubMedGoogle Scholar
  23. 23.
    Matsui T, Nakata N, Nagai S, Nakatani A, Takahashi M, Momose T, et al. Inflammatory cytokines and hypoxia contribute to 18F-FDG uptake by cells involved in pannus formation in rheumatoid arthritis. J Nucl Med. 2009;50(6):920–6.CrossRefPubMedGoogle Scholar
  24. 24.
    Oettmeier R, Abendroth K. Osteoarthritis and bone: osteologic types of osteoarthritis of the hip. Skeletal Radiol. 1989;18:165–74.CrossRefPubMedGoogle Scholar
  25. 25.
    Radin EL, Rose RM. Role of subchondral bone in the initiation and progression of cartilage damage. Clin Orthop. 1986;213:34–40.PubMedGoogle Scholar
  26. 26.
    Burr DB. The importance of subchondral bone in osteoarthrosis. Curr Opin Rheumatol. 1998;10:256–62.CrossRefPubMedGoogle Scholar
  27. 27.
    Goker B, Sumner DR, Hurwitz DE, Block JA. Bone mineral density varies as a function of the rate of joint space narrowing in the hip. J Rheumatol. 2000;27:735–8.PubMedGoogle Scholar
  28. 28.
    Lane NE, Nevitt MC. Osteoarthritis, bone mass, and fractures: how are they related? Arthritis Rheum. 2002;46:1–4.CrossRefPubMedGoogle Scholar
  29. 29.
    Hayami T, Pickarski M, Wesolowski GA, McLane J, Bone A, Destefano J, et al. The role of subchondral bone remodeling in osteoarthritis: reduction of cartilage degeneration and prevention of osteophyte formation by alendronate in the rat anterior cruciate ligament transection model. Arthritis Rheum. 2004;50(4):1193–206.CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society of Nuclear Medicine 2010

Authors and Affiliations

  • Yusuke Umemoto
    • 1
    Email author
  • Takushi Oka
    • 2
  • Tomio Inoue
    • 2
  • Tomoyuki Saito
    • 1
  1. 1.Department of Orthopaedic SurgeryYokohama City University Graduate School of MedicineYokohamaJapan
  2. 2.Department of RadiologyYokohama City University Graduate School of MedicineYokohamaJapan

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